Positive association between striatal serotonin level and abnormal involuntary movements in chronic L-DOPA-treated hemiparkinsonian rats
Positive association between striatal serotonin level and abnormal involuntary movements in chronic L-DOPA-treated hemiparkinsonian rats
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DOI：
10.1016/j.brainresbull.2010.12.006
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发表时间：
2011-02-01
影响因子：
3.8
通讯作者：
Koh, Hyun C.
中科院分区：
文献类型：
--
作者：
Gil, Suk J.;Park, Chang H.;Koh, Hyun C.
虽然左旋多巴代表了帕金森病的标准治疗，但长期治疗可能会受到左旋多巴诱导的运动障碍（LID）的影响，伴随运动反应性的不利波动和进行性失控。在这里，我们表明，在大鼠与6-羟基多巴胺诱导的病变的正中前脑束，LID与5-HT水平。用左旋多巴（6 mg/kg）和苄丝肼（15 mg/kg）连续3周诱发大鼠异常不自主运动（AIMS），结果表明，慢性左旋多巴治疗后，大鼠损伤侧纹状体多巴胺（DA）和5-羟色胺（5-HT）水平明显改变。纹状体DA和5-羟色胺（5-HT）水平呈负相关，AIM与DA水平呈强正相关，与5-HT水平呈负相关。与其他AIM亚型相比，轴向AIM与DA和5-HT水平的相关性更强，而运动性AIM则完全没有显着相关性。此外，纹状体5-HT与AIM比纹状体DA水平更强（负）相关。这些结果表明，5-HT有助于LID和纹状体DA（积极）和5-HT（消极）影响LID的严重程度。我们认为通过策略性地改变5-羟色胺系统可能减轻长期左旋多巴治疗的不良反应。(C)2010年爱思唯尔公司All rights reserved.
Although L-DOPA represents the standard of care in Parkinson's disease, long-term treatment may be compromised by L-DOPA-induced dyskinesia (LID), with adverse fluctuations in motor responsiveness and progressive loss of control. Here we show that in rats with 6-hydroxydopamine-induced lesions of the median forebrain bundle, LID correlates with 5-HT levels. Rats were treated with L-DOPA (6 mg/kg) and benserazide (15 mg/kg) daily for 3 weeks to induce the development of abnormal involuntary movements (AIMS).After this chronic L-DOPA treatment, the lesion side of the rats displayed significant changes in striatal dopamine (DA) and 5-HT levels. Striatal DA and 5-hydroxytryptamine (5-HT) levels were inversely correlated, and AIMs were strongly positively correlated DA levels and negatively correlated with 5-HT levels. Axial AIMs were more strongly correlated with DA and 5-HT levels than were the other AIMs subtypes, while locomotive AIMs showed no significant correlation at all. In addition, striatal 5-HT was more strongly (negatively) correlated with the AIMs than striatal DA levels. These results demonstrate that 5-HT contributes to LID and that both striata DA (positively) and 5-HT(negatively) affect the severity of LID. We suggest that by strategic modification of the serotonin system it may be posible to attenuate the adverse effect of chronic L-DOPA therapy. (C) 2010 Elsevier Inc. All rights reserved.